isopropyl diethylphosphonylmethanesulphonate | 114086-63-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机膦酸及其衍生物
• 英文名称: isopropyl diethylphosphonylmethanesulphonate
• 英文别名: (Diethoxyphosphinyl)methanesulfonic acid, 1-methylethyl ester；propan-2-yl diethoxyphosphorylmethanesulfonate
• CAS: 114086-63-4
• 化学式: C₈H₁₉O₆PS
• 分子量: 274.275
• InChiKey: AOPXJIPTFPNSBM-UHFFFAOYSA-N

物化性质

• 沸点：
  387.7±25.0 °C(Predicted)
• 密度：
  1.217±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  16
• 可旋转键数：
  8
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  87.3
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  溴代十四烷 、 isopropyl diethylphosphonylmethanesulphonate 在 NaH 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以0.30 g (31%)的产率得到1-(Diethoxyphosphinyl)pentadecanesulfonic acid, 1-methylethyl ester
  参考文献：
  名称：

  Methods of using .alpha.-phosphonosulfonate squalene synthetase

  摘要：

  提供了抑制酶角鲨烯合酶并从而抑制胆固醇生物合成的.alpha.-磷酸磺酸酯化合物。这些化合物的化学式为##STR1##其中R.sup.2为OR.sup.5或R.sup.5a；R.sup.3和R.sup.5独立地为H、烷基、芳基烷基、芳基或环烷基；R.sup.5a为H、烷基、芳基烷基或芳基；R.sup.4为H、烷基、芳基、芳基烷基或环烷基；Z为H、卤素、低烷基或低烯基；R.sup.1为至少含有7个碳原子的疏水基团，为烷基、烯基、炔基、混合烯基-炔基、芳基、芳基烷基、环烷基、环烷基烷基、杂环芳基、杂环芳基烷基、环杂环烷基、环杂环烷基烷基；如上所述；包括磷酸(亚磷酸)和/或磺酸的药用可接受盐和/或前药酯。

  公开号：

  US05470845A1
• 作为产物：
  描述：

  甲磺酸异丙酯 、 氯磷酸二乙酯 在 正丁基锂 作用下， 生成 isopropyl diethylphosphonylmethanesulphonate
  参考文献：
  名称：

  通过维蒂格-霍纳反应合成α，β-不饱和磺酸盐

  摘要：

  描述了通过Wittig-Horner反应合成α，β-不饱和磺酸盐的一般和实用方法（25个实例）。与盐2和羰基化合物的反应不是很立体选择性。相反，与酯1的反应得到高产率的（E）-α，β-不饱和磺酸酯。

  DOI：

  10.1016/s0040-4020(01)87688-2

文献信息

• [EN] PYRROLIDINE-FUSED THIADIAZINE DIOXIDE COMPOUNDS AS BACE INHIBITORS, COMPOSITIONS, AND THEIR USE<br/>[FR] COMPOSÉS DE DIOXYDE DE THIADIAZINE FUSIONNÉE À LA PYRROLIDINE EN TANT QU'INHIBITEURS DE BACE, COMPOSITIONS ET LEUR UTILISATION
  申请人：MERCK SHARP & DOHME

  公开号：WO2012138590A1

  公开（公告）日：2012-10-11

  In its many embodiments, the present invention provides provides certain iminothiadiazine dioxide compounds, including compounds Formula (I): and tautomers and stereoisomers thereof, and pharmaceutically acceptable salts of said compounds, said tautomeros and said stereoisomers, wherein each of W, Z, R1H, R2, R3, R4, ring A, ring B, m, n, p, and- L1- is as defined herein. The novel compounds of the invention have surprisingly been found to exhibit properties which are expected to render them advantageous as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including Alzheimer's disease, are also disclosed.

  在其众多实施方式中，本发明提供了特定的咪唑噻二唑二氧化物化合物，包括化合物式（I）中的化合物及其互变异构体和立体异构体，以及所述化合物的药用可接受盐，所述互变异构体和所述立体异构体，其中W、Z、R1H、R2、R3、R4、环A、环B、m、n、p和-L1-的每一个在此处定义。本发明的新化合物被发现具有出乎意料的性质，预计将使它们在作为BACE抑制剂和/或用于治疗和预防与之相关的各种病理方面具有优势。还公开了包括一种或多种此类化合物（单独或与一种或多种其他活性剂的组合）的制备和使用方法，包括治疗阿尔茨海默病的药物组合。
• .alpha.-phosphonosulfonate squalene synthetase inhibitors
  申请人：——

  公开号：US05712396A1

  公开（公告）日：1998-01-27

  .alpha.-Phosphonosulfonate compounds are provided which inhibit the enzyme squalene synthetase and thereby inhibit cholesterol biosynthesis. These compounds have the formula ##STR1## wherein R.sup.2 is OR.sup.5 or R.sup.5a ; R.sup.3 and R.sup.5 are independently H, alkyl, arylalkyl, aryl or cycloalkyl; R.sup.5a is H, alkyl, arylalkyl or aryl; R4 is H, alkyl, aryl, arylalkyl, or cycloalkyl;, Z is H, halogen, lower alkyl or lower alkenyl; and R.sup.1 is a lipophilic group which contains at least 7 carbons and is alkyl, alkenyl, alkynyl, mixed alkenyl-alkynyl, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, cycloheteroalkyl, cycloheteroalkylalkyl; as further defined above; including pharmaceutically acceptable salts and or prodrug esters of the phosphonic (phosphinic) and/or sulfonic acids.

  提供了抑制齿烯合成酶并从而抑制胆固醇生物合成的.alpha.-磷酸磺酸盐化合物。这些化合物的化学式为##STR1##其中R.sup.2为OR.sup.5或R.sup.5a; R.sup.3和R.sup.5分别为H、烷基、芳基烷基、芳基或环烷基；R.sup.5a为H、烷基、芳基烷基或芳基；R4为H、烷基、芳基、芳基烷基或环烷基；Z为H、卤素、低烷基或低烯基；R.sup.1为至少含有7个碳的脂溶性基团，可以是烷基、烯基、炔基、混合烯基-炔基、芳基、芳基烷基、环烷基、环烷基烷基、杂芳基、杂芳基烷基、环杂基、环杂基烷基；还包括上述定义的磷酸（亚磷酸）和/或磺酸的药学上可接受的盐和/或前药酯。
• .alpha.-phosphonosulfonate squalene synthetase inhibitors and method
  申请人：Bristol-Myers Squibb Company

  公开号：US05567841A1

  公开（公告）日：1996-10-22

  .alpha.-Phosphonosulfonate compounds are provided which inhibit the enzyme squalene synthetase and thereby inhibit cholesterol biosynthesis. These compounds have the formula ##STR1## wherein R.sup.2 is OR.sup.5 or R.sup.5a ; R.sup.3 and R.sup.5 are independently H, alkyl, arylalkyl, aryl or cycloalkyl; R.sup.5a is H, alkyl, arylalkyl or aryl; R.sup.4 is H, alkyl, aryl, arylalkyl, or cycloalkyl;, Z is H, halogen, lower alkyl or lower alkenyl; and R.sup.1 is a lipophilic group which contains at least 7 carbons and is alkyl, alkenyl, alkynyl, mixed alkenyl-alkynyl, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, cycloheteroalkyl, cycloheteroalkylalkyl; as further defined above; including pharmaceutically acceptable salts and or prodrug esters of the phosphonic (phosphinic) and/or sulfonic acids.

  提供了α-磷酸磺酸化合物，可以抑制齿烯合酶酶并从而抑制胆固醇生物合成。这些化合物的化学式为##STR1##其中R.sup.2是OR.sup.5或R.sup.5a;R.sup.3和R.sup.5分别是H、烷基、芳基烷基、芳基或环烷基；R.sup.5a是H、烷基、芳基烷基或芳基；R.sup.4是H、烷基、芳基、芳基烷基或环烷基；Z是H、卤素、低烷基或低烯基；R.sup.1是至少含有7个碳的亲脂性基团，可以是烷基、烯基、炔基、混合烯炔基、芳基、芳基烷基、环烷基、环烷基烷基、杂芳基、杂芳基烷基、环杂烷基、环杂烷基烷基等，包括磷酸（亚磷酸）和/或磺酸的药物可接受的盐和/或前药酯。
• Methods of using .alpha.-phosphonosulfonate squalene synthetase
  申请人：Bristol-Myers Squibb Company

  公开号：US05470845A1

  公开（公告）日：1995-11-28

  .alpha.-Phosphonosulfonate compounds are provided which inhibit the enzyme squalene synthetase and thereby inhibit cholesterol biosynthesis. These compounds have the formula ##STR1## wherein R.sup.2 is OR.sup.5 or R.sup.5a ; R.sup.3 and R.sup.5 are independently H, alkyl, arylalkyl, aryl or cycloalkyl; R.sup.5a is H, alkyl, arylalkyl or aryl; R.sup.4 is H, alkyl, aryl, arylalkyl, or cycloalkyl;, Z is H, halogen, lower alkyl or lower alkenyl; and R.sup.1 is a lipophilic group which contains at least 7 carbons and is alkyl, alkenyl, alkynyl, mixed alkenyl-alkynyl, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, cycloheteroalkyl, cycloheteroalkylalkyl; as further defined above; including pharmaceutically acceptable salts and or prodrug esters of the phosphonic (phosphinic) and/or sulfonic acids.

  提供了抑制酶角鲨烯合酶并从而抑制胆固醇生物合成的.alpha.-磷酸磺酸酯化合物。这些化合物的化学式为##STR1##其中R.sup.2为OR.sup.5或R.sup.5a；R.sup.3和R.sup.5独立地为H、烷基、芳基烷基、芳基或环烷基；R.sup.5a为H、烷基、芳基烷基或芳基；R.sup.4为H、烷基、芳基、芳基烷基或环烷基；Z为H、卤素、低烷基或低烯基；R.sup.1为至少含有7个碳原子的疏水基团，为烷基、烯基、炔基、混合烯基-炔基、芳基、芳基烷基、环烷基、环烷基烷基、杂环芳基、杂环芳基烷基、环杂环烷基、环杂环烷基烷基；如上所述；包括磷酸(亚磷酸)和/或磺酸的药用可接受盐和/或前药酯。
• Synthesis of α, β-unsaturated sulphonates via the wittig-horner reaction
  作者：Juan Carlos Carretero、Marc Demillequand、Léon Ghosez

  DOI：10.1016/s0040-4020(01)87688-2

  日期：1987.1

  A general and practical method of synthesis of α,β-unsaturated sulphonates (25 examples) by the Wittig-Horner reaction is described. Reactions with the salts 2 and carbonyl compounds are not very stereoselective. On the contrary, reactions with esters 1 gave high yields of (E)-α,β-unsaturated sulphonic esters.

  描述了通过Wittig-Horner反应合成α，β-不饱和磺酸盐的一般和实用方法（25个实例）。与盐2和羰基化合物的反应不是很立体选择性。相反，与酯1的反应得到高产率的（E）-α，β-不饱和磺酸酯。